Characteristics of successful expansion of tumor-infiltrating lymphocytes from colorectal cancer liver metastasis

Abstract Adoptive cell therapy (ACT) utilizing tumor-infiltrating lymphocytes (TILs) has emerged as a successful treatment modality for various malignancies. However, TILs cultured from colorectal cancer (CRC) liver metastasis remain underexplored. Fifteen CRC liver metastasis tissues underwent init...

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Main Authors: Jina Baek, Gyuheon Choi, GunHee Lee, Hyun Lee, Gyungyub Gong, Hye Seon Park, Chae-Lyul Lim, Joo Young Kim, Hee Jin Lee
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-85892-5
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author Jina Baek
Gyuheon Choi
GunHee Lee
Hyun Lee
Gyungyub Gong
Hye Seon Park
Chae-Lyul Lim
Joo Young Kim
Hee Jin Lee
author_facet Jina Baek
Gyuheon Choi
GunHee Lee
Hyun Lee
Gyungyub Gong
Hye Seon Park
Chae-Lyul Lim
Joo Young Kim
Hee Jin Lee
author_sort Jina Baek
collection DOAJ
description Abstract Adoptive cell therapy (ACT) utilizing tumor-infiltrating lymphocytes (TILs) has emerged as a successful treatment modality for various malignancies. However, TILs cultured from colorectal cancer (CRC) liver metastasis remain underexplored. Fifteen CRC liver metastasis tissues underwent initial expansion (IE) of TILs and rapid expansion (REP). Histologic examination including the level of stromal TILs and Klintrup-Mäkinen score, were assessed by pathologists and deep learning-derived spatial analysis. We performed correlation analysis between expanded TILs and histopathologic factors. All cases exhibited successful IE, with a mean IE TIL count per fragment and total IE TIL per case of 2.59 ± 2.79e5 cells and 167.79 ± 126.97e5 cells, respectively. Five cases underwent REP, with a median fold change of 3,610 (range, 1,136–4,925). The median CD4+/CD8 + ratio in IE TILs and REP TILs were 3.66 and 0.68, respectively. A significant correlation was observed between the mean number of expanded TILs per fragment and KM score (p = 0.022). Successful expansion of TILs from CRC liver metastasis was achieved. Assessment of KM score may serve as a predictive tool for the obtainable TILs before IE. These findings lay the groundwork for future studies to establish effective ACT in patients with metastatic CRC.
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spelling doaj-art-560c456aa6d146809590a081c89d684f2025-01-12T12:22:20ZengNature PortfolioScientific Reports2045-23222025-01-0115111010.1038/s41598-025-85892-5Characteristics of successful expansion of tumor-infiltrating lymphocytes from colorectal cancer liver metastasisJina Baek0Gyuheon Choi1GunHee Lee2Hyun Lee3Gyungyub Gong4Hye Seon Park5Chae-Lyul Lim6Joo Young Kim7Hee Jin Lee8Department of Pathology, Asan Medical Center, University of Ulsan College of MedicineDepartment of Pathology, Asan Medical Center, University of Ulsan College of MedicineDepartment of Pathology, Asan Medical Center, University of Ulsan College of MedicineDepartment of Pathology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of KoreaDepartment of Pathology, Asan Medical Center, University of Ulsan College of MedicineNeogenTC Corp.NeogenTC Corp.Department of Pathology, Chung-Ang University Hospital, College of Medicine, Chung-Ang UniversityDepartment of Pathology, Asan Medical Center, University of Ulsan College of MedicineAbstract Adoptive cell therapy (ACT) utilizing tumor-infiltrating lymphocytes (TILs) has emerged as a successful treatment modality for various malignancies. However, TILs cultured from colorectal cancer (CRC) liver metastasis remain underexplored. Fifteen CRC liver metastasis tissues underwent initial expansion (IE) of TILs and rapid expansion (REP). Histologic examination including the level of stromal TILs and Klintrup-Mäkinen score, were assessed by pathologists and deep learning-derived spatial analysis. We performed correlation analysis between expanded TILs and histopathologic factors. All cases exhibited successful IE, with a mean IE TIL count per fragment and total IE TIL per case of 2.59 ± 2.79e5 cells and 167.79 ± 126.97e5 cells, respectively. Five cases underwent REP, with a median fold change of 3,610 (range, 1,136–4,925). The median CD4+/CD8 + ratio in IE TILs and REP TILs were 3.66 and 0.68, respectively. A significant correlation was observed between the mean number of expanded TILs per fragment and KM score (p = 0.022). Successful expansion of TILs from CRC liver metastasis was achieved. Assessment of KM score may serve as a predictive tool for the obtainable TILs before IE. These findings lay the groundwork for future studies to establish effective ACT in patients with metastatic CRC.https://doi.org/10.1038/s41598-025-85892-5Colorectal cancerLiver metastasisTumor-infiltrating lymphocytesAdoptive cell therapy
spellingShingle Jina Baek
Gyuheon Choi
GunHee Lee
Hyun Lee
Gyungyub Gong
Hye Seon Park
Chae-Lyul Lim
Joo Young Kim
Hee Jin Lee
Characteristics of successful expansion of tumor-infiltrating lymphocytes from colorectal cancer liver metastasis
Scientific Reports
Colorectal cancer
Liver metastasis
Tumor-infiltrating lymphocytes
Adoptive cell therapy
title Characteristics of successful expansion of tumor-infiltrating lymphocytes from colorectal cancer liver metastasis
title_full Characteristics of successful expansion of tumor-infiltrating lymphocytes from colorectal cancer liver metastasis
title_fullStr Characteristics of successful expansion of tumor-infiltrating lymphocytes from colorectal cancer liver metastasis
title_full_unstemmed Characteristics of successful expansion of tumor-infiltrating lymphocytes from colorectal cancer liver metastasis
title_short Characteristics of successful expansion of tumor-infiltrating lymphocytes from colorectal cancer liver metastasis
title_sort characteristics of successful expansion of tumor infiltrating lymphocytes from colorectal cancer liver metastasis
topic Colorectal cancer
Liver metastasis
Tumor-infiltrating lymphocytes
Adoptive cell therapy
url https://doi.org/10.1038/s41598-025-85892-5
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